overview of clinical research in oncology Flashcards
clinical trials
experiments to determine value of treatment
no matter how good your pre-clinical data is you cannot?
predict drug will work in human beings
what are the 2 key components of clinical trials?
(1) results are required to support conclusion instead of reasoning
(2) experiments must be planned and conducted under controlled conditions to give definitive answers to well defined questions. If not done right, you will not get right answer.
in essence what is a protocol?
explains what you want to do and how do you want to test drug
protocol defines?
question to be answered
number of patients needed to answer question
treatment and evaluation of a well defined set of patients
why does drug have to be tested on healthy patient?
to see result of drug without any other factors interfering with it
performance status that patient must have for clinical trials
70% or above
70% you are home and can take care of yourself
must be self dependent
patient inclusion criteria for clinical trials?
must have good kidney function good hepatic (liver) function good heart function good hematopoietic function basically good function of vital organs
patient exclusion criteria for clinical trials
any chronic infections no HIV no other type of cancer no other malignancies pregnancy, lactating, gyn complications if drug tested interacted with other drug on market
what is the scientific key to clinical trials?
the statistics
research
systematic investigation including research development, testing and evaluation to develop or contribute to generalized knowledge
human subject
living (no autopsy) individual that an investigator conducting research obtains data through intervention with individual or identifiable private information
patient have the right to withdraw as stated in informed consent. How do they correctly withdraw?
withdraw must be in writing and cannot be by word of mouth
HIPPA
policy on who has access of patient records
how do you get a certificate of confidentiality to be immune to court order of releasing patient information?
write a letter to NIH asking for certificate of confidentiality and the IRB will even ask you to get one if information is very sensitive.
the review by IRB will be on?
annual, semiannual basis
objective of phase I trial?
determine dose appropriate in phase II trials
patient of phase I trial
pts are of advanced disease resistant to standard therapy: good functional status and they have all tumor types to test on
phase I trial dose escalation
start at 1/10 LD50 in dogs and then increase dose every 3-6 patients using modified fibonacci progression
grades of toxicity
0 1 2 3 4
In pharmacokinetics of phase I trial, what does the area under the curve represent for measuring serum concentration within hours of drug dose?
area under the curve is how long drug is prevalent in blood serum and cancer exposed
what is the purpose of studying pharmacokinetics in phase I trial?
to reach dose that is minimally toxic in phase I
Phase II clinical trial
test efficacy of MTD (maximal tolerable dose) of a drug
does the drug work?
pick one tumor type respondent in phase I and may be efficacious for this drug in phase II
minimal prior therapy and good KPS
show agent active in favorable group before trying in more debilitated pretreated patients
phase II clinical trial objective
determine if drug has anti-tumor activity - measure response rate.
phase III clinical trials endpoints
survival and patient welfare, not tumor shrinkage
response in phase II trial does not garuntee ?
prolonged survival
phase III clinical trial determines?
if drug makes patient with cancer live longer
who writes protocol?
experienced investigator at cancer center and company doctors
protocol takes into account?
animal data and decides best regimen for progression, pharmacokinetics, and dynamics
purpose of IRB is to?
protect vulnerable subjects
Nurenberg code
crimes against humanity
Helsinky declaration
conduct of clinical research
ethical issues for phase I?
phase I - subject with incurable disease
toxicity vs benefit
study vs therapeutic intent - low chance of response, must not mislead
patient wants to please doctor
conflict of interest - publish, financial
ethical issue for phase II?
still low probability of benefit of survival
oncologist’s biases
less complex - looking for efficacy, less likelihood of unexpected toxicity
phase III looks for ??
efficacy (length of survival) and not shrinkage of tumor
phase III ethical issues
no true neutrality
permission to randomize patient- doctor gives up primary responsibility
what is the only ethical way to answer important questions and forward progress of medical care?
conducting phase III study
NIH toxicity criteria 0-4
0 - normal
1 - abnormal
2- no requirement of treatment or aid
3 - abnormality correctible with aid or treatment
4- severe abnormality, not correctable by aid or treatment
subject headings for protocols
introduction of story
objective
pt selection
study design
treatment plan
drug info
toxicities monitored and dose modifications
clinical and lab data and calendar
criteria to evaluate treatment; defined endpoint
stats; data forms
informed consent, investigators, IRB chair, phone #s
response evaluation criteria in solid tumors (RECIST)
measurable disease - at least 1 measurable lesion
measurable lesions of cancer- lesion measured in at least 1 dimension with longest diameter
non-measurable lesions of cancer- all other lesions with longest diameter
what is the minimum KPS for clinical trial protocols?
70% or higher
70% patient stays home and can take care of self
karnofsky perfomance status (KPS)
0% = death 50% = hospitalization 70% = stays home and minimum for protocols 100% = normal, no complaints, no signs of disease
ECOG/Zubrod performance status
0 - asymptomatic
1 - symptomatic but ambulatory
2- sympotomatic, <50% in bed during the day and is minimum for protocols
3- symptomatic, >50% in bed, but not bedbound
4 - bedbound
5 - death
